A Phase 1 randomized, open-label clinical trial to evaluate the effect of a far-infrared emitting patch on local skin perfusion, microcirculation and oxygenation.

Far-infrared radiation (FIR) has been investigated for reduction of pain and improvement of dermal blood flow. The FIRTECH patch is a medical device designed to re-emit FIR radiated by the body. This phase 1 study was conducted to evaluate the local effects of the FIRTECH patch on local skin perfusion, microcirculation and oxygenation. This prospective, randomized, open-label, parallel designed study admitted 20 healthy participants to a medical research facility for treatment for 31 h on three anatomical locations. During treatment, imaging assessments consisting of laser speckle contrast imaging, near-infrared spectroscopy, side-stream dark-field microscopy, multispectral imaging and thermography were conducted regularly on patch-treated skin and contralateral non-treated skin. The primary endpoint was baseline perfusion increase during treatment on the upper back. Secondary endpoints included change in baseline perfusion, oxygen consumption and temperature of treated versus untreated areas. The primary endpoint was not statistically significantly different between treated and non-treated areas. The secondary endpoints baseline perfusion on the forearm (least square means [LSMs] difference 2.63 PU, 95% CI: 0.97, 4.28), oxygen consumption (LSMs difference: 0.42 arbitrary units [AUs], 95% CI: 0.04, 0.81) and skin temperature (LSMs difference 0.35°C, 95% CI: 0.16, 0.6) were statistically significantly higher in treated areas. Adverse events observed during the study were mild and transient. The vascular response to the FIRTECH patch was short-lived suggesting a non-thermal vasodilatory effect of the patch. The FIRTECH patch was well tolerated, with mild and transient adverse events observed during the study. These results support the therapeutic potential of FIR in future investigations.

A tactile pain evaluation scale for persons with visual deficiencies.

OBJECTIVE: Pain evaluation scales often rely on the sense of sight. There is so far no pain assessment scale designed specifically for persons with visual impairment. DESIGN: This study aims to validate a tactile pain evaluation scale, Visiodol (Copyright Prof Pickering), in blind or visually impaired persons, by correlation with a numeric pain scale. SETTING: The study took place at University Hospital Clermont-Ferrand, France. METHODS: Pain intensity for a range of thermal stimuli (Pathway Medoc) was evaluated with Visiodol and a numeric pain scale. Secondary outcomes, including pain thresholds, catastrophizing, emotion, and quality of life, were compared in persons who were blind or visually impaired and in sighted persons. Lin's concordance correlation coefficient was estimated. Weighted Cohen's κ accounted for degrees of disagreement between scales with 95% confidence intervals (95% CI). SUBJECTS: Sixteen healthy sighted and 21 healthy nonsighted volunteers (n = 13 congenital, n = 8 acquired) were included. RESULTS: Lin's correlation coefficient for repeated data was 0.967 (95% CI, 0.956-0.978; P < 0.001) for visually impaired participants, with a good agreement at each temperature plateau. A weighted Cohen's κ of 0.90 (95% CI, 0.84-0.92) and 92.9% percentage of agreement for visually impaired participants were satisfactory. Pain perception, psychological components, and quality of life were more impaired in persons who were blind or visually impaired than in sighted persons. CONCLUSIONS: This study validates Visiodol, a tactile scale for persons who are blind or visually impaired, and addresses health care inequalities in the context of pain evaluation. Visiodol will now be tested in a larger population of patients to give the millions of persons worldwide who are blind or visually impaired an option for pain intensity evaluation in clinical situations. TRIAL REGISTRATION: French National Agency for the Safety of Medicines and Healthcare Products (2018-A03370-55) and www.ClinicalTrials.gov (NCT03968991).

Effects of Totum-63 on glucose homeostasis and postprandial glycemia: a translational study.

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

Real-Life Management Pathways for Chronic Peripheral Neuropathic Pain at Tertiary Pain Clinics in France.

OBJECTIVE: Peripheral neuropathic pain (PNP) represents a major public health issue. Severe or refractory cases warrant tertiary multidisciplinary management, but little information is available about real-life care pathways. The primary objective of this cross-sectional, observational study was to investigate the pathways of patients with PNP consulting for the first time or followed for less than 1 year in French tertiary specialized pain clinics. METHODS: PNP was diagnosed with the NeuPSIG algorithm. Data collected included demographics, pain characteristics, and details of management before and after the study visit (e.g., drug and non-drug treatment, nature of medical visits), as well as time to referral to a pain clinic and time to a diagnosis of PNP. Factors associated with delayed referral or diagnosis were analyzed with multivariate analysis. RESULTS: A total of 404 patients with PNP (age 55.8 ± 15.6 years, 60.3% females, 78.3% retired or unemployed, pain duration 43.4 ± 68.9 months) were enrolled by 84 pain specialists. Pain affected mainly the lower limbs (53.5%) and was predominantly related to surgery or trauma (59.4%). Primary care management was characterized by a high proportion of conventional analgesics (60.7%). Time to referral to a pain clinic was 43.4 ± 68.9 months since pain onset and 20.1 ± 39.4 months since the diagnosis of PNP. Delayed referral to a pain clinic was independently predicted by the clinical specialty of the referring doctor and by male gender. CONCLUSIONS: This study highlights the need for accessible guidance for non-pain specialists to improve their diagnostic and management skills and for faster referral of patients with PNP to tertiary pain clinics.

Risk factors and comorbidities associated with magnesium deficiency in pregnant women and women with hormone-related conditions: analysis of a large real-world dataset.

BACKGROUND: An accumulating body of literature indicates that magnesium deficiency is associated with a number of hormone-related conditions (HRC) in women, and epidemiological studies are needed to assess its prevalence and risk factors. Here, we present a secondary analysis of data pooled from four large observational studies that assessed magnesium deficiency among pregnant women and women with HRC across the Russian Federation. METHODS: The main objective of this analysis was to estimate the prevalence of magnesium deficiency in this population and to describe risk factors and comorbidities associated with low serum magnesium. Univariate logistic regression analysis was performed to identify the risk factors and comorbid conditions associated with an increased risk of low serum magnesium level. RESULTS: A total of 983 pregnant women and 9444 women with HRC were eligible for analysis. Prevalence of hypomagnesemia (magnesium serum level cut-off < 0.66 mmol/L/< 0.8 mmol/L) was 34.0%/78.9% in pregnant women and 21.4%/54.8% in women with HRC. The highest prevalence of magnesium deficiency was observed for osteoporosis and climacteric syndrome. Risk factors included diastolic blood pressure, previous pregnancy complications, infections and edema for pregnant women, and age, body mass index, and various comorbidities for women with HRC. CONCLUSIONS: These results confirm the high prevalence of hypomagnesemia in pregnant women and women with HRC and underline the importance of routine screening, since risk factors are mostly non-specific.

Non-specific analgesia during a clinical trial in fibromyalgia.

BACKGROUND: When patients suffering from fibromyalgia undergo a therapeutic trial, a non-negligible part of analgesia is not explained by the drug itself. The mechanisms of this non-specific effect need to be understood. MATERIALS AND METHODS: We undertook secondary analyses of a double-blind randomized trial in fibromyalgia patients in which 100 mg/day milnacipran was not found superior to placebo. Data from 49 patients belonging to both groups were pooled. Both before treatment and one month after treatment, all patients underwent a CaNTAB® neuropsychological test (related to spatial planning, reaction time, decision-making and risk-taking, and ability to name objects), and measurements of sensation and pain thresholds to heat and cold, supraliminal heat pain threshold, punctuate mechanical pain threshold and temporal summation, mechanical allodynia to skin brushing, and response to conditioned pain modulation. We studied the baseline predictors of analgesia and the indicators of change associated to analgesia separately. A stepwise approach was used to select the factors to enter into the final ANCOVAs, in which age, body mass index, treatment group and pain at baseline were covariates. RESULTS: No baseline predictor of non-specific analgesia other than pain at baseline was found to be predictive. Conversely, several neuropsychological (higher performance) or psychophysical (lower sensitivity) changes correlated with analgesia in unadjusted analyses. Multivariable analyses identified increases in warm/heat thermal thresholds and an increased ability to name objects, as factors associated with analgesia. CONCLUSIONS: The changes observed concomitantly to non-specific pain analgesia might be related to mild changes in brain functioning, based on convergent literature data.

Ketamine and Magnesium for Refractory Neuropathic Pain: A Randomized, Double-blind, Crossover Trial.

BACKGROUND: Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive-emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks. METHODS: A randomized, double-blind, crossover, placebo-controlled study (NCT02467517) included 20 patients with neuropathic pain. Each ketamine-naïve patient received one infusion every 35 days in a random order: ketamine (0.5 mg/kg)/placebo or ketamine (0.5 mg/kg)/magnesium sulfate (3g) or placebo/placebo.The primary endpoint was the area under the curve of daily pain intensity for a period of 35 days after infusion. Secondary endpoints included pain (at 7, 15, 21 and 28 days) and health-related, emotional, sleep, and quality of life questionnaires. RESULTS: Daily pain intensity was not significantly different between the three groups (n = 20) over 35 days (mean area under the curve = 185 ± 100, 196 ± 92, and 187 ± 90 pain score-days for ketamine, ketamine/magnesium, and placebo, respectively, P = 0.296). The effect size of the main endpoint was -0.2 (95% CI [-0.6 to 0.3]; P = 0.425) for ketamine versus placebo, 0.2 (95% CI [-0.3 to 0.6]; P = 0.445) for placebo versus ketamine/magnesium and -0.4 (95% CI [-0.8 to 0.1]; P = 0.119) for ketamine versus ketamine/magnesium. There were no significant differences in emotional, sleep, and quality of life measures. During placebo, ketamine, and ketamine/magnesium infusions, 10%, 20%, and 35% of patients respectively reported at least one adverse event. CONCLUSIONS: The results of this trial in neuropathic pain refuted the hypothesis that ketamine provided pain relief at 5 weeks and cognitive-emotional benefit versus placebo and that a combination with magnesium had any additional analgesic effect.

Paracetamol and Pain Modulation by TRPV1, UGT2B15, SULT1A1 Genotypes: A Randomized Clinical Trial in Healthy Volunteers.

BACKGROUND: The influence of the genetic polymorphism of enzymes and receptors involved in paracetamol metabolism and mechanism of action has not been investigated. This trial in healthy volunteers investigated the link between paracetamol pain relief and the genetic polymorphism of 23 enzymes and receptors. DESIGN: This randomized double-blind crossover controlled pilot study took place in the Clinical Pharmacology Department, University Hospital, Clermont-Ferrand, France. Forty-seven Caucasian volunteers were recruited. The trial consisted of two randomized sessions one week apart with oral paracetamol or placebo, and pain changes were evaluated with mechanical pain stimuli. The genetic polymorphism of 23 enzymes and receptors was studied, and correlations were made with pain relief. All tests are two-sided with a type I error at 0.05. RESULTS: Paracetamol was antinociceptive compared with placebo (222 ± 482 kPaxmin vs 23 ± 431 kPaxmin; P = 0.0047), and the study showed 30 paracetamol responders and 17 paracetamol nonresponders. Responders were characterized by TRPV1rs224534 A allele, UGT2B15rs1902023 TT genotype, and SULT1A1rs9282861 GG genotype (P < 0.05 for all). These findings confirm for the first time the involvement of a specific TRPV1 rs224534 variant in paracetamol antinociception. They also reveal a new antinociceptive role for specific variants of hepatic phase II enzymes associated with paracetamol metabolism. CONCLUSIONS: The study warrants larger clinical trials on these potential genomic markers of paracetamol analgesia in patients. Confirmation of the present findings would open the way to effective individualized pain treatment with paracetamol, the most commonly used analgesic worldwide.

Efficacy and Safety of Magnesium for the Management of Chronic Pain in Adults: A Systematic Review.

Chronic pain is a highly prevalent and complex health problem that is associated with a heavy symptom burden, substantial economic and social impact, and also, very few highly effective treatments. This review examines evidence for the efficacy and safety of magnesium in chronic pain. The previously published protocol for this review was registered in International Prospective Register of Systematic Reviews (PROSPERO), MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched until September 2018. We included randomized controlled trials (RCTs) comparing magnesium (at any dose, frequency, or route of administration) with placebo using participant-reported pain measures. A total of 9 RCTs containing 418 participants were included. Three studies examined neuropathic pain (62 participants), 3 examined migraines (190 participants), 2 examined complex regional pain syndrome (86 participants), and 1 examined low back pain with a neuropathic component (80 participants). Heterogeneity of included studies precluded any meta-analyses. No judgment could be made about safety because adverse events were inconsistently reported in the included studies. Evidence of analgesic efficacy from included studies was equivocal. However, reported efficacy signals in some of the included trials provide a rationale for more definitive studies. Future, larger-sized trials with good assay sensitivity and better safety assessment and reporting, as well as careful attention to formulations with optimal bioavailability, will serve to better define the role of magnesium in the management of chronic pain.

Electrochemical Skin Conductance and Quantitative Sensory Testing on Fibromyalgia.

BACKGROUND: An impairment of the peripheral nervous system has been suggested in fibromyalgia (FM). Noninvasive distal electrochemical skin conductance (ESC) has been studied little so far when combined with quantitative sensory testing (QST) in patients with FM. METHODS: This study (clinicaltrials.gov NCT03347669) included 50 female patients with FM and 50 matched healthy volunteers (HVs). ESC (measured in microsiemens [µS] with Sudoscan), as well as psychological, quality of life, sleep, and social characteristics, were assessed in both groups. In a subgroup of 24 patients with FM and 24 HVs, QST of cold and warm detection and pain thresholds and diffuse noxious inhibitory controls (DNICs) were explored. Statistical analysis was performed for a 2-sided type I error at 5%. RESULTS: Between patients with FM and HVs, ESC values differed (71.4 ± 11.2 µS vs. 74.4 ± 10.3 µS, respectively; P = 0.003), especially on the dominant hand (P = 0.03), where more patients with FM had ESC values < 66 µS than did HVs (P = 0.046). No difference was observed on feet. In patients with FM, all collected characteristics were impaired (P < 0.001), DNICs were less functional, detection thresholds occurred later, and pain thresholds occurred earlier. No correlation was observed between ESC and DNICs or with any parameter. CONCLUSION: This study shows that the sudomotor function is significantly impaired in patients with FM, especially on the dominant hand. This occurs in parallel with adjustments of detection and pain thresholds in the context of deficient spinal pain modulation. ESC values combined with QST values are relevant in the context of patients with FM and need to be explored further in this nociception-autonomic system intertwining.

Hormonal Status and Cognitivo-Emotional Profile in Real-Life Patients With Neuropathic Pain: A Case Control Study.

BACKGROUND: The specific impact of neuropathic pain and recommended neuropathic pain treatments on the hormonal and immune status of patients has been so far poorly explored. This study aimed at studying, in real life, the hypothalamic-pituitary-adrenal axis and the cytokine profile of patients with neuropathic pain. It also explored their links with cognition, emotion, quality of life, and drug treatment. METHODS: This prospective study (clinicaltrials.gov NCT01543425) included 60 patients with neuropathic pain and 60 age- and gender-matched healthy volunteers after obtaining signatures of informed consent. A number of parameters were measured: adrenocorticotropic hormone, cortisol, cortisol awakening response, dehydroepiandrosterone sulphate, sex hormone binding globulin, testosterone, 17-ß-estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, cytokines, brain-derived neurotrophic factor, and vitamin D. Psychological parameters were assessed by questionnaires. RESULTS: Patients with neuropathic pain had lower levels of adrenocorticotropic hormone (P = 0.009) and dehydroepiandrosterone sulphate (P < 0.001) than controls, and the cortisol awakening response was impaired. Patients were more depressed and anxious (P < 0.001) and had a diminished quality of life (P < 0.001), which was influenced by cytokines (P = 0.0067) and testosterone (P = 0.028). Antidepressants and antiepileptics appeared to interfere with testosterone and cognitivo-emotional domains. CONCLUSION: An impairment of the hormonal status and of the immune system was observed in patients. It identified testosterone as a potential pivotal mediator between antidepressants/antiepileptics and quality of life. Further studies must address the exact impact of different types of drugs on central effects, of gender differences, and of the immune system of neuropathic pain.

Reliability Study in Five Languages of the Translation of the Pain Observational Scale Algoplus.

Objective: Acute pain is frequent and underestimated in older persons, especially when they suffer from cognitive impairment. Algoplus is an observational scale for acute pain evaluation, validated in French in older persons with communication disorders. We present the validation by an international expert team of the Algoplus scale in five languages: English, Spanish, Italian, Portuguese, and Turkish. Methods: A total of 181 older consecutive patients were included in five countries (Spain, Australia, Italy, Portugal, and Turkey). Test-retest and inter-rater reliabilities were determined by weighted kappa coefficient for each item and internal consistency by Kuder-Richardson-20 (KD). Results: Regarding test-retest reliability, the kappa coefficient for the five items ranged from 0.68 to 0.84. Inter-rater reliability kappa values ranged from 0.64 to 0.82. Internal consistency was indicated at a KD greater than 0.6. Satisfaction was good to excellent for all teams. Results show that reliability tests are good to excellent for all items of Algoplus. Conclusions: This study shows evidence that Algoplus is an acceptable, reproducible, reliable, and easy-to-use tool. It provides a unique opportunity to include the translated Algoplus scale in daily assessment of older persons with communication disorders in many countries.

[Ketamine and chronic pain: A narrative review of its efficacy and its adverse events]. / Kétamine et douleur chronique : une revue narrative de son efficacité et sécurité.

Ketamine is frequently used in the management of refractory chronic pain. To date, the level of proof in the literature on ketamine in this type of indication is generally poor and physicians have no consensus or recommendation to support their practice. This narrative review is an update on literature data assessing the efficacy and safety of ketamine in chronic pain. The electronic search of the Medline, PubMed, Google Scholar and Cochrane databases identified a total of 61 articles including randomized and non-randomized trials and 14 international reviews. In view of these data, it is difficult to conclude on the effectiveness of ketamine in this type of indication and on its safety due to the heterogeneity of practice in terms of doses, routes, duration and frequency of administration and especially a lack of clinical trials with a high level of evidence.

[Acute analgesic effect of paracetamol in primary care: Incomplete evidence]. / Effet antalgique aigu du paracétamol en soins primaires : des preuves incomplètes.

This meta-analysis assessed the analgesic effect of a single oral dose of paracetamol versus placebo in adults, in primary care. Parallel randomized studies were searched on MEDLINE®, CENTRAL®, and EMBASE®. We found five studies on sore throat (842 patients) and 12 studies on headache (3433 patients). None related to low back pain. Regardless of the outcome, paracetamol was superior to placebo (number need to treat [NNT]=4-5; standardized mean difference [SMD]=0.51-0.92). Additional clinical trials in other primary care conditions, like low back pain, must be conducted.

Intervention Study with Algoplus® : A Pain Behavioral Scale for Older Patients in the Emergency Department.

OBJECTIVES: Evaluation of acute pain is often difficult in older patients admitted to the Emergency Department (ED), and self-evaluation of pain is not always possible. This observational study evaluates how the systematic use of Algoplus® , a validated behavioral scale, could improve pain management of older persons admitted to the ED. METHOD: The intervention study (NCT 02258503) took place in 4 steps in the ED, University Hospital Clermont-Ferrand, France. Pain assessment and analgesics prescription were collected from medical files for 3 months. For 6 months, the whole staff of the ED were trained on pain assessment and to use Algoplus® scale (3-same as step 1). To evaluate the intervention, pain assessment and analgesics prescription were compared before and after implementation by 2-sided tests with a type I error set at α = 0.05. RESULTS: The intervention led to systematic pain evaluation with Algoplus® in 100% of patients (≥ 75 years old, n = 434) and was completed by numeric rating scale (NRS) and other evaluations. Pearson's correlation between NRS ≥ 3 and Algoplus® < 2 was 0.61. Prescription of analgesics (+6%) especially opioids increased nonsignificantly but was similar for all patients whatever the evaluation. CONCLUSIONS: The systematic introduction of Algoplus® scale in the ED allowed a change in practice by improving evaluation and management of pain in patients ≥ 75 years old, especially when difficult to be evaluated. Algoplus® allowed an objective levelling of analgesics prescription in all admitted patients. It also promoted field action to improve pain management in ED.

The Algoplus Score to Assess Acute Postoperative pain in Elderly patients-A Pilot Observational Study.

Standard verbal or analogue scales may not be accurate to assess acute postoperative pain in elderly patients. This study was designed to field test the Algoplus tool, developed specifically for this population and based on observation of patient behavior. Prospective, observational cohort. Single center, French University hospital. Forty-eight patients, aged over 65, scheduled for surgery under general anesthesia, and observed on admission to the postanesthesia care unit, immediately after extubation, during the different steps of analgesic intervention (demand, relief with intravenous opioid titration, plus intermediate measures when relevant), and either at discharge or 3 hours after admission. A numerical rating scale (NRS) was used to guide analgesia. The Algoplus score and the state of alertness or sedation were noted. NRS scores and Algoplus scores were significantly related, and both scores significantly decreased under the effect of analgesia, but the correlation was low. In early observations, the Algoplus score was higher than that predicted by the NRS score, in relation to residual sedation. Female gender tended to lower the Algoplus score compared to the NRS score. When the NRS score exceeded 3/10, indicating the need for analgesic intervention, the Algoplus score was generally lower than the recommended trigger for analgesia (2/5). These results are promising, but further evidence of a clinical benefit to the use of Algoplus for acute postoperative pain is needed. In future studies, scoring should be adjusted to take into account the time from extubation, the state of sedation, and the patient's gender in order to interpret results.

Cognitive function in older patients with postherpetic neuralgia.

BACKGROUND AND AIMS: Neuropathic pain has been shown to be accompanied by cognitive impairment, but the specific impact of postherpetic neuropathic pain on cognitive processes has not been explored. This study aims to evaluate the impact of pain on several domains of cognition in older patients with postherpetic neuralgia (PHN). METHODS: This cross-sectional study (clinicaltrial.gov NCT 00989040) included 84 individuals after signature of informed consent. PARTICIPANTS: 42 patients with PHN and 42 healthy volunteers. Of the 42 PHN patients, 21 received systemic treatment (antidepressants, anticonvulsants, opiates) and 21 had topical treatment with the 5% lidocaine medicated plaster. All participants performed a panel of four cognitive tests: reaction time, semantic memory, decision-making, and visual memory (Cantab, Cambridge). RESULTS: Forty men and 44 women with a mean age of 72 ± 8 years participated. Each PHN patient was matched by age and gender with a healthy volunteer. Vigilance, decision-making, and semantic memory were significantly impaired (P < 0.05) in patients on systemic treatment, especially with antidepressants, while no significant changes were noted between the lidocaine plaster group and their matched controls of healthy volunteers. CONCLUSION: This study shows the deleterious effect of systemic PHN treatment on several domains of cognition. Cognitive impairment associated with pain and antidepressants may be reversed by topical pain management. Topical treatment with 5% lidocaine medicated plaster is a valuable alternative for pain alleviation and maintains cognitive integrity in this vulnerable population.

Osteoporosis treatment and pain relief: A scoping review.

BACKGROUND AND OBJECTIVE: Anti-osteoporosis (OP) drugs have been suggested to contribute to pain reduction during OP management. This scoping review aimed at mapping the literature on pain relief with anti-OP drugs in OP treatment. DATABASES AND DATA TREATMENT: Medline, Pubmed and Cochrane databases were searched by two reviewers with keywords combinations. Randomized controlled and real-life English studies, pain as an endpoint, antiosteoporosis drugs were inclusion criteria. Case reports, surveys, comment letters, conference abstracts, animal studies and grey literature were excluded. Predetermined data were extracted by two reviewers and disagreement solved through discussion. RESULTS: A total of 130 articles were identified, 31 publications were included, 12 randomized clinical trials and 19 observational studies. Pain reduction was assessed by different tools: Visual Analogue Scale, Verbal Rating Scale, Facial Scale or as a domain of quality of life questionnaires including Short form 8, 36, mini-OP, Japanese OP, Qualeffo, Roland Morris Disability questionnaires. Collective data show that anti-OP drugs may display an analgesic effect that may be linked to the local mode of action of drugs on bone and consecutive modulation of pain sensitization. The methodology of the studies showed a heterogeneity of endpoints, comparators, statistical approaches and follow-up duration. CONCLUSION: Considering the limitations of the literature, there is a need for more rigorous trials and larger real-life studies taking into account the recommendations published for research in rheumatology and in pain medicine. The identification of responders, patient subtypes, and of analgesic-effect doses would allow optimization and individualization for pain relief in patients with OP. SIGNIFICANCE STATEMENT: This scoping review shows that anti-OP drugs may improve pain and quality of life of patients with OP. The heterogeneity in design, choice of endpoints, methodology, comparators and follow-up duration of included randomized clinical trials and real-life studies does not allow so far to identify a predominant antiosteoporosis drug or an optimal dosage for pain relief. These gaps need to be addressed and warrant further research in the future for optimizing pain improvement in the course of OP drug treatment.

Is the Capsaicin 179 mg (8% w/w) Cutaneous Patch an Appropriate Treatment Option for Older Patients with Peripheral Neuropathic Pain?

Introduction: Capsaicin 179 mg (8% weight per weight) cutaneous patch ("capsaicin patch") is a recommended topical treatment for peripheral neuropathic pain (PNP). In older patients, topical treatments may be preferred over systemic treatments, but data specific to the older population are scarce. Methods: We conducted pooled analyses of multiple clinical trials to evaluate efficacy and safety of capsaicin patch in older patients. The analysis of efficacy included four randomized, double-blind, 12-week studies with similar trial design comparing a single treatment of capsaicin 179 mg cutaneous patch vs low-dose control patch in post-herpetic neuralgia. For the safety evaluation, data were pooled from 18 interventional studies in which capsaicin patch was used in PNP with varying etiologies. Results: Capsaicin patch had similar analgesic efficacy in elderly (n=582) and non-elderly patients (n=545) in terms of change from baseline to 2-12 weeks in the 11-point numeric pain rating scale (NPRS) score for average pain over the previous 24 hours. In both age groups, decrease in NPRS score was significantly greater with capsaicin patch vs control. Older patients treated with capsaicin patch were significantly more likely than those in the control group to achieve responder status (ie mean decrease in NPRS score from baseline to week 2-12 of at least 30% or ≥2 points): 36.1% vs 27.1% (odds ratio [OR] [95% CI] 1.52 [1.06, 2.18]; P=0.0231) and 33.1% vs 20.9% (OR [95% CI] 1.90 [1.30, 2.78]; P=0.0009) for active treatment vs control group, respectively. Similar proportions of non-elderly patients (n=2,311) and elderly patients (n=537) treated with capsaicin patch experienced treatment-emergent adverse events (TEAEs) (81.6% and 78.1%, respectively) and serious TEAEs (8.2% and 7.2%), with application-site reactions the most common TEAEs in both groups. Conclusion: The capsaicin patch was equally efficacious and well tolerated in older patients as in younger patients.

Peripheral neuropathic pain is a common challenge among the elderly, yet effective treatments for this age group remain underexplored. This research focuses on the use of a high-concentration capsaicin patch, a specialized treatment for this type of pain. The patch, which is applied directly to the affected skin area, has been shown to reduce pain significantly for up to 12 weeks. This analysis of multiple clinical trials showed that the high-concentration capsaicin patch significantly reduced pain intensity and was well tolerated in older patients with peripheral neuropathic pain.

Systematic review and co-ordinate based meta-analysis to summarize the utilization of functional brain imaging in conjunction with human models of peripheral and central sensitization.

BACKGROUND AND OBJECTIVE: Functional magnetic resonance imaging, in conjunction with models of peripheral and/or central sensitization, has been used to assess analgesic efficacy in healthy humans. This review aims to summarize the use of these techniques to characterize brain mechanisms of hyperalgesia/allodynia and to evaluate the efficacy of analgesics. DATABASES AND DATA TREATMENT: Searches were performed (PubMed-Medline, Cochrane, Web of Science and Clinicaltrials.gov) to identify and review studies. A co-ordinate based meta-analysis (CBMA) was conducted to quantify neural activity that was reported across multiple independent studies in the hyperalgesic condition compared to control, using GingerALE software. RESULTS: Of 217 publications, 30 studies met the inclusion criteria. They studied nine different models of hyperalgesia/allodynia assessed in the primary (14) or secondary hyperalgesia zone (16). Twenty-three studies focused on neural correlates of hyperalgesic conditions and showed consistent changes in the somatosensory cortex, prefrontal cortices, insular cortex, anterior cingulate cortex, thalamus and brainstem. The CBMA on 12 studies that reported activation coordinates for a contrast comparing the hyperalgesic state to control produced six activation clusters (significant at false discovery rate of 0.05) with more peaks for secondary (17.7) than primary zones (7.3). Seven studies showed modulation of brain activity by analgesics in five of the clusters but also in four additional regions. CONCLUSIONS: This meta-analysis revealed substantial but incomplete overlap between brain areas related to neural mechanisms of hyperalgesia and those reflecting the efficacy of analgesic drugs. Studies testing in the secondary zone were more sensitive to evaluate analgesic efficacy on central sensitization at brainstem or thalamocortical levels. SIGNIFICANCE: Experimental pain models that provide a surrogate for features of pathological pain conditions in healthy humans and functional imaging techniques are both highly valuable research tools. This review shows that when used together, they provide a wealth of information about brain activity during pain states and analgesia. These tools are promising candidates to help bridge the gap between animal and human studies, to improve translatability and provide opportunities for identification of new targets for back-translation to animal studies.